摘要目的:研究腺病毒介导的白细胞介素37（IL-37）对人非小细胞肺癌（NSCLC）A549细胞生长及放射敏感性的影响，探讨IL-37作为新型放疗增敏剂的可能性。方法:选择人NSCLC细胞株A549，将A549细胞分为3组：正常A549细胞（对照组）、空病毒转染的A549细胞[NC组，细胞感染复数（MOI）为100]、Ad-IL-37组（含IL-37的腺病毒转染A549细胞，MOI为100）。用蛋白质印迹法检测3组细胞IL-37蛋白表达情况；将3组细胞同时应用4 Gy照射剂量进行照射，四甲基偶氮唑盐（MTT）法检测吸光度（A）值，观察A549细胞增殖情况；流式细胞术观察受照射后各组A549细胞周期变化；蛋白质印迹法检测照射后各组细胞凋亡相关蛋白（bax、bcl-2、Caspase-3、Survivin）表达情况。结果:对照组IL-37的相对表达水平为0.17±0.04，NC组为0.29±0.14，Ad-IL-37组为1.17±0.23（F=24.263，P=0.001）。照射后24 h时3组A值差异无统计学意义（F=2.587，P=0.160），照射后48、72、96、108 h时A值差异均具有统计学意义（F值分别为21.662、33.635、33.663、31.909，P值分别为0.005、0.001、0.001、0.001）；照射后24 h时NC组和Ad-IL-37组细胞增殖抑制率差异无统计学意义（t=1.620，P=0.247），照射后48、72、96、108 h时两组细胞增殖抑制率差异均有统计学意义（t值分别为5.414、7.233、15.306、19.035，P值分别为0.032、0.019、0.004、0.003）。IL-37联合可影响细胞周期的变化，对照组S期细胞比例为（36.4±1.0）%，NC组为（31.3±0.6）%，Ad-IL-37组为（27.2±2.9）%（F=12.96，P=0.007），对照组G 2/M细胞比例为（20.5±0.8）%，NC组为（24.7±2.9）%，Ad-IL-37组为（41.4±4.1）%（F=27.92，P=0.001）。IL-37能上调照射的A549细胞促凋亡相关因子bax、Caspase-3蛋白水平（F值分别10.31、14.51，P值均为0.01），下调抑凋亡因子bcl-2、Survivin蛋白的表达（F值分别8.95、5.52，P值分别0.02、0.04）。 结论:IL-37可抑制A549细胞生长，具有潜在的放射增敏作用，这一作用可能通过影响肿瘤细胞的凋亡产生。

abstractsObjective:To analyze the effects of adenovirus-mediated interleukin-37 (IL-37) on the growth and radiosensitivity of human non-small cell lung cancer (NSCLC) cell line A549, and to explore the possibility of IL-37 as a new radiosensitizer.Methods:Human NSCLC cell line A549 was used as the research object. A549 cells were divided into three groups: normal A549 cells (control group), empty virus transfected A549 group [NC group, the multiple of infection (MOI) was 100], Ad-IL-37 group (A549 cells were transfected by adenovirus with IL-37, MOI was 100). The expression of IL-37 protein in three groups was detected by Western blot. The three groups were irradiated with 4 Gy irradiation dose at the same time. The methyl thiazolyl tetrazolium (MTT) method was used to detect the absorbance (A) values and observe the proliferation of A549 cells; flow cytometry was used to observe the phase changes of A549 cells in each group after irradiation; Western blot was used to detect the expressions of apoptosis-related proteins (bax, bcl-2, Caspase-3, and Survivin) in each group after irradiation.Results:The expression level of IL-37 in the control group was 0.17±0.04, NC group was 0.29±0.14, and Ad-IL-37 group was 1.17±0.23 (F = 24.263, P = 0.001); there was no statistical difference in A values among the three groups at 24 h after irradiation (F = 2.587, P = 0.160), while the differences of A values among the three groups at 48, 72, 96, 108 h after irradiation were statistically significant (F values were 21.662, 33.635, 33.663, and 31.909, P values were 0.005, 0.001, 0.001, and 0.001, respectively). There was no significant difference in the cell proliferation inhibition rate between NC group and Ad-IL-37 group at 24 h after irradiation (t = 1.620, P = 0.247), while the differences were statistically significant at 48, 72, 96, 108 h after irradiation (t values were 5.414, 7.233, 15.306, and 19.035, P values were 0.032, 0.019, 0.004, and 0.003, respectively). The combination of IL-37 and radiation could affect the cell cycle, the proportion of S-phase cells was (36.4±1.0)% in the control group, (31.3±0.6)% in the NC group, and (27.2±2.9)% in the Ad-IL-37 group (F = 12.96, P = 0.007), and the proportion of in G 2/M-phase cells was (20.5±0.8)% in the control group, (24.7±2.9)% in the NC group, and (41.4±4.1)% in the Ad-IL-37 group, (F = 27.92, P = 0.001). IL-37 could up-regulate the expressions of pro-apoptotic factors bax and Caspase-3 proteins in A549 cells after irradiation (F values were 10.31 and 14.51, P values were both 0.01), and down-regulate the expressions of apoptotic factors bcl-2 and Survivin proteins (F values were 8.95 and 5.52, P values were 0.02 and 0.04). Conclusion:IL-37 could inhibit the growth of human NSCLC cell line A549 and has potential radiosensitization effects, which may be caused by affecting the apoptosis of tumor cells.